Diabetes and Kidney Clinical Trials

Several clinical trials presented at the American Diabetes Association meeting in June 2019 show promise in terms of improved renal function in type 2 diabetes patients.

Ertugliflozin, a type 2 diabetes drug manufactured as Steglatro by Merck (White House Station, NJ) and in partnership with Pfizer (New York, NY) appeared to protect renal function among this patient population, according to data pooled from two randomized trials, reported EndocrinologyAdvisor.com. Participants were divided into groups taking ertugliflozin 5 mg, ertugliflozin 15 mg, glimepiride, or placebo. The drug is a sodium-glucose co-transporter 2 (SGLT2) inhibitor.

At baseline, mean estimated glomerular filtration rate (eGFR) was 88.2 mL/min/1.73 m2. After 6 weeks, patients receiving ertugliflozin 5 or 15 mg showed greater reductions in eGFR compared with patients not receiving ertugliflozin (-2.3 and -2.7 vs -0.7 mL/min/1.73 m2, respectively). However, over 104 weeks, the eGFR values increased with the ertugliflozin group compared with controls, which suggested renal function preservation.

Dulaglutide (brand name Trulicity [Eli Lilly, Indianapolis, IN]) results were also shared during the meeting. The GLP-1 receptor agonist slowed renal function decline in some type 2 diabetes patients with poor kidney function. The researchers also announced they found a biomarker that predicted which patients exhibit decline in kidney function.

In the AWARD-7 study, among patients with macroalbuminuria at enrollment, only 7.1% of those patients on a weekly injection of 1.5 mg dulaglutide had 40% or greater eGFR decline, progression to ESKD, or kidney-related death, compared with 22.2 % of patients on insulin glargine.

“The benefits of dulaglutide were driven by results in this group of participants [excreting large amounts of albumin], who’s a group at very high risk for CKD progression,” said researcher Katherine Tuttle, MD, of the University of Washington, Seattle, during a press conference about the findings.

In the CREDENCE trial, which enrolled 4401 patients with type 2 diabetes and CKD, canagliflozin (Invokana [Janssen, Beerse, Belgium]), a SGLT2 inhibitor, lowered the risk for progression to ESKD and other primary outcome factors by 30% compared with the placebo arm. The primary outcome was a composite of ESKD (dialysis, transplantation, or a sustained eGFR of less than 15 mL/min/1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. The risk of the renal-specific composite outcome of ESKD, doubling of serum creatinine, and death from renal causes was lowered by 34% in the canagliflozin group compared with placebo. According to the American Diabetes Association, the CREDENCE trial is the first study in 18 years to show a drug can reduce cardiovascular and renal outcomes in people with type 2 diabetes and CKD, regardless of their previous history of cardiovascular disease.

Cherney D, et al. Two-year effects of ertugliflozin on renal function. Presented at: American Diabetes Association 79th Scientific Sessions, June 7–11, 2019; San Francisco, CA. Poster 1197-P. Diabetes 2019; 68(Supplement 1); https://doi.org/10.2337/db19-1197-P.

Tuttle KR, et al. Chronic Kidney Disease (CKD) outcomes with dulaglutide (DU) vs. insulin glargine (IG) in type 2 diabetes (T2D) and moderate-to-severe CKD by albuminuria status: AWARD-7. American Diabetes Association 79th Scientific Sessions. Diabetes 2019; 68 (Supplement 1); https://doi.org/10.2337/db19-233-OR

Perkovic V, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; DOI: 10.1056/NEJMoa1811744.

July 2019 (Vol. 11, Number 7)